MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group

DuBois, Steven G.; Mody, Rajen; Naranjo, Arlene; Ryn, Collin J Van; Russ, Douglas; Oldridge, Derek A.; Kreissman, Susan G.; Baker, David L.; Parisi, Marguerite T.; Shulkin, Barry L.; Bai, Harrison X.; Diskin, Sharon J.; Batra, Vandana; Maris, John M.; Park, Julie R.; Matthay, Katherine K.; Yanik, Gregory A.

doi:10.1002/pbc.26545

Cited by 32 publications

(25 citation statements)

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“…Neuroblastoma is one of the most common cancers in children, and its incidence has increased by 7% every 10 years between 1985 and 2015 [22,24]. Advances have been made in the diagnosis and therapy of NB, including better radiological imaging, cytological, biochemical, and molecular techniques; however, the 5-year survival rate of patients with high-risk NB remains below 50% [11,25,26]. Many factors contribute to this disappointing outcome, most notably the persistence of chemoresistant minimal residual disease (MRD), which is responsible for disease recurrence in > 50% of patients with high-risk NB [1,14,24,27].…”

Section: Discussionmentioning

confidence: 99%

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Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

Wang²,

Jiang

et al. 2020

BMC Cancer

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Background: Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence. Methods: A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children's Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence. Results: Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL. Conclusions: High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.

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Section: Discussionmentioning

confidence: 99%

“…Treatment of NB is based on risk stratification and typically includes surgery, chemotherapy, radiation, and immunotherapy in high risk patients [8][9][10][11]. Prevention of tumor recurrence is particularly difficult in patients with high-risk NB, for whom the 5-year survival rate is less than 50% [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

Wang²,

Jiang

et al. 2020

BMC Cancer

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“…This survival rate is mainly due to tumor relapse or regrowth caused by the activation of chemoresistant minimal residual disease (MRD) . To evaluate the therapeutic response and disease status of NB patients, several MRD detection methods, including 131 I‐metaiodobenzylguanidine ( 131 I‐MIBG), have a high detection sensitivity in NB primary tumors and bone or bone marrow metastasis . However, 131 I‐MIBG detection is complicated and requires a long time.…”

Section: Introductionmentioning

confidence: 99%

“…1,[3][4][5] To evaluate the therapeutic response and disease status of NB patients, several MRD detection methods, including 131 I-metaiodobenzylguanidine ( 131 I-MIBG), have a high detection sensitivity in NB primary tumors and bone or bone marrow metastasis. 6,7 However, 131 I-MIBG detection is complicated and requires a long time. Therefore, the clinical evaluation of a precise diagnosis of MRD by molecular pathology in NB patients remains to be established.…”

Section: Introductionmentioning

confidence: 99%

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Wang

Wang²,

et al. 2018

Cancer Medicine

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To evaluate plasma cell‐free DNA (cfDNA) as a promising biomarker for neuroblastoma (NB) tumor burden. Seventy‐nine eligible patients with newly diagnosed NB were recruited from Beijing Children's Hospital between April 2016 and April 2017. Additionally, from September 2011 to June 2017, 79 patients with stable NB were evaluated with a median follow‐up time of 21 months. Approximately 2 mL of peripheral blood was drawn upon enrollment, and plasma cfDNA levels were measured via quantitative polymerase chain reaction (qPCR). Total cfDNA analysis was performed using the long interspersed nuclear element 1 (LINE‐1) 79 bp fragment, and DNA integrity was calculated by the ratio of the LINE‐1 300 bp fragment to the LINE‐1 79 bp fragment. A total of 79 NB patients with a median age of 36 months comprised the group of newly diagnosed NB patients. The main primary tumor site was the retroperitoneal and adrenal region (81%). Three or more metastatic sites were found in 17.7% of patients. Stable NB patients older than 18 months comprised 98.7% of the stable NB patients. Neuron‐specific enolase (NSE), lactate dehydrogenase (LDH), and cfDNA levels were dramatically increased in the newly diagnosed NB patients and significantly different from those in the stable NB patients. Moreover, the concentration of cfDNA was much higher in patients with larger tumors. By analyzing the area under the receiver operator characteristic (ROC) curve (AUC), the areas of total cfDNA, NSE, and LDH levels were 0.953, 0.929, and 0.906, respectively. The sensitivity and specificity data clarified that the level of circulating cfDNA in plasma can be considered as a reliable biomarker for describing tumor load in NB. The plasma cfDNA concentration was as good as the levels of LDH and NSE to discriminate the tumor burden in children with NB.

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“…Treatment of NB is based on risk stratification and typically includes surgery, chemotherapy, radiation, and immunotherapy [8][9][10][11]. Prevention of tumor recurrence is particularly difficult in patients with high-risk NB, for whom the 5-year survival rate is less than 50% [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

Wang²,

Jiang

et al. 2020

Preprint

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Background Neuroblastoma is the third-most common cancer in children. The high rate of tumor recurrence accounts for a low survival rate in high risk neuroblastoma. Therefore it is clinically of extreme importance to find an effective biomarker for alerting disease recurrence.Methods Total 116 high risk neuroblastoma patients were recruited in Beijing Children's Hospital from February, 2015 to December, 2017. All patients had received multiple-disciplinary treatment, then went into maintenance treatment phase after evaluation. Blood samples were collected to quantify plasma cell-free DNA (cfDNA) at time points of the beginning of maintenance treatment, every three months afterwards, and diagnosis of recurrence.Results Results showed that 36 high risk neuroblastoma patients developed recurrence during maintenance treatment. The plasma cfDNA concentration was significantly higher in recurrence than in event-free patients (29.34 ng/ml VS 10.32 ng/ml). The time span of cfDNA level higher than 29 ng/ml was consistently detected ahead of recurrence at mean of 0.55 months. The ROC analysis showed that AUC was 0.825, optimal sensitivity and specificity of 80.6% and 71.3% respectively, at cfDNA level of 12.93 ng/ml.Conclusions We concluded that high level of plasma cfDNA could serve as a promising molecular marker to alert recurrence disease in high risk neuroblastoma children.

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MIBG avidity correlates with clinical features, tumor biology, and outcomes in neuroblastoma: A report from the Children's Oncology Group

Cited by 32 publications

References 25 publications

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

Plasma cell‐free DNA quantification is highly correlated to tumor burden in children with neuroblastoma

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

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